There is growing evidence that early life events play an important role in the development of breast cancer, and the onset of puberty is thought be a key event in influencing subsequent breast cancer risk. If it is known that lifestyle, environmental, or genetic factors influence pubertal development, this may potentially provide another area for strategies to prevent breast cancer and promote health of young girls. In order to examine the role of environmental and genetic determinants of puberty, we propose to conduct a prospective cohort study of 400 girls who are members of the Kaiser Permanente of Northern California (KPNC) Medical Care Program. We will enroll girls who are aged 7 or 8 y at baseline, and follow them as they mature sexually. Our sampling frame will be the KPNC Infant Cohort file, which documents every birth that has occurred within KPNC since 1990. We will enroll girls who were born in and are current members of KPNC, thus enabling access to substantial clinical information regarding prenatal care, birth records, and infant and childhood clinical visits. We will recruit from girls who live in Matin County, San Francisco, and selected Alameda County communities to facilitate in-clinic exams. This population of girls is also diverse racially and ethnically. At baseline and annually thereafter, we plan clinic visits to assess Tanner Stage for breast and pubic hair development, and to collect information by interview regarding various factors that may influence age at onset of these hallmarks of puberty. We are interested in: anthropomettic factors such as weight, height, body fatness, or growth trajectory; food and nutrient intake; physical activity; and exposure to tobacco smoke and alcohol. We propose to collect and store biospecimens annually. Blood will be collected to enable investigation of exposure to long-lived organohalogen compounds including polychlorinated biphenyls and polybrominated diphenyl ethers. DNA from blood samples will be extracted and pooled for genotyping for polymorphisms in genes related to metabolism of sex steroid hormones or exogenous exposures that may influence pubertal development. Urine will be collected to measure levels of estradiol and gonadotropins, as an alternative measure of sexual maturation. After 5-6 years of follow-up, we anticipate that about 319 and 304 girls will have transitioned through Tanner Stage 2 for breast (B2) or pubic hair (P2) development, respectively, and 151 girls will have experienced onset of menses. This provides adequate power to detect relative risk of about 1.5 for exposures with prevalence of 0.2 for B2 or P2, and about 1.7 for onset of menses. With a larger cohort or pooling of data from other Centers, we should have adequate power to detect associations or interactions with public health or clinical significance.